Objective Magnetoreception, the remarkable ability of diverse animals to sense and utilize the geomagnetic field for orientation and navigation, remains a molecularly unresolved mystery in sensory biology. The putative magnetoreceptor (MagR, previously known as IscA1) is a highly conserved iron-sulfur protein implicated in both magnetoreception and iron metabolism; however, the functional diversity among its cross-species homologs remains poorly understood. Cellular morphology is a key genetically determined trait that can be altered through genetic or environmental modifications—a process known as cell morphology engineering. Constructing engineered cells with specific morphological features and magnetic sensitivity to achieve remote, non-invasive magnetic modulation represents a crucial goal in this field with significant application potential. Therefore, this study aims to systematically investigate the effects of MagR heterologous expression on bacterial morphology and magnetic sensing capabilities, screen for MagR-based magnetically sensitive morphology engineering pathways, and reveal the underlying molecular mechanisms. Methods We systematically screened 28 MagR homologous genes from diverse prokaryotic and animal taxa to evaluate their expression and corresponding phenotypic effects in Escherichia coli (E. coli). To compare the differential magnetic responses among bacteria expressing various recombinant MagR proteins, we utilized high-throughput automated bright-field microscopic imaging and scanning electron microscopy (SEM). Furthermore, comprehensive biochemical and biophysical characterizations of iron and iron-sulfur cluster binding were performed using Ferrozine colorimetric assays, electron paramagnetic resonance (EPR) spectroscopy, ultraviolet-visible (UV-Vis) absorption, and circular dichroism (CD) spectroscopy. Additionally, 100 mT static magnetic field (SMF) exposure experiments were conducted to assess magnetically tunable phenotypes, while the intrinsic magnetic properties of purified MagR proteins were directly measured using a superconducting quantum interference device (SQUID) magnetometer. Results Our results demonstrated that the heterologous expression of MagR homologs induced varying degrees of bacterial filamentation. From this comprehensive screen, two distinct morphological patterns were identified: hydra (Hydra vulgaris) MagR (hyMagR) promoted uniform cell elongation and filamentation, exhibiting robust magnetic sensitivity manifested as significantly enhanced filamentation under the 100 mT SMF. In contrast, pigeon (Columba livia) MagR (clMagR) induced only low-frequency, extreme filamentation (sporadically exceeding 80 μm) with a relatively weaker magnetic morphological response. Mechanistically, our data unambiguously proved that these phenotypic differences are primarily driven by distinct iron redox preferences rather than total cellular iron accumulation. Specifically, hyMagR preferentially binds ferrous iron (Fe²⁺), whereas clMagR favors ferric iron (Fe³⁺) and forms more stable iron-sulfur clusters. Intriguingly, although SQUID magnetometry showed that purified clMagR exhibited approximately five-fold higher mass magnetic susceptibility than hyMagR, its cellular magnetic response was weaker. We hypothesize that the Fe²⁺-preferred intracellular environment associated with hyMagR overexpression primes the cell for enhanced generation of reactive oxygen species (ROS) via the Fenton reaction. Exposure to an SMF synergizes with this primed redox state, triggering the bacterial SOS response and upregulating cell division inhibitors to efficiently induce uniform filamentation. Conclusion Our findings identify the Fe²⁺/Fe³⁺ redox state as a critical determinant of MagR-mediated morphological remodeling and magnetic responsiveness. This discovery suggests a potential strategy for engineering magnetically responsive cellular systems for synthetic biology applications, and provides a plausible framework, which potentially combines intrinsic protein magnetism with redox-state modulation, for further investigating the evolutionary mechanisms of MagR-mediated magnetoreception.

Objective Magnetoreception, the remarkable ability of diverse animals to sense and utilize the geomagnetic field for orientation and navigation, remains a molecularly unresolved mystery in sensory biology. The putative magnetoreceptor (MagR, previously known as IscA1) is a highly conserved iron-sulfur protein implicated in both magnetoreception and iron metabolism; however, the functional diversity among its cross-species homologs remains poorly understood. Cellular morphology is a key genetically determined trait that can be altered through genetic or environmental modifications—a process known as cell morphology engineering. Constructing engineered cells with specific morphological features and magnetic sensitivity to achieve remote, non-invasive magnetic modulation represents a crucial goal in this field with significant application potential. Therefore, this study aims to systematically investigate the effects of MagR heterologous expression on bacterial morphology and magnetic sensing capabilities, screen for MagR-based magnetically sensitive morphology engineering pathways, and reveal the underlying molecular mechanisms. Methods We systematically screened 28 MagR homologous genes from diverse prokaryotic and animal taxa to evaluate their expression and corresponding phenotypic effects in Escherichia coli (E. coli). To compare the differential magnetic responses among bacteria expressing various recombinant MagR proteins, we utilized high-throughput automated bright-field microscopic imaging and scanning electron microscopy (SEM). Furthermore, comprehensive biochemical and biophysical characterizations of iron and iron-sulfur cluster binding were performed using Ferrozine colorimetric assays, electron paramagnetic resonance (EPR) spectroscopy, ultraviolet-visible (UV-Vis) absorption, and circular dichroism (CD) spectroscopy. Additionally, 100 mT static magnetic field (SMF) exposure experiments were conducted to assess magnetically tunable phenotypes, while the intrinsic magnetic properties of purified MagR proteins were directly measured using a superconducting quantum interference device (SQUID) magnetometer. Results Our results demonstrated that the heterologous expression of MagR homologs induced varying degrees of bacterial filamentation. From this comprehensive screen, two distinct morphological patterns were identified: hydra (Hydra vulgaris) MagR (hyMagR) promoted uniform cell elongation and filamentation, exhibiting robust magnetic sensitivity manifested as significantly enhanced filamentation under the 100 mT SMF. In contrast, pigeon (Columba livia) MagR (clMagR) induced only low-frequency, extreme filamentation (sporadically exceeding 80 μm) with a relatively weaker magnetic morphological response. Mechanistically, our data unambiguously proved that these phenotypic differences are primarily driven by distinct iron redox preferences rather than total cellular iron accumulation. Specifically, hyMagR preferentially binds ferrous iron (Fe²⁺), whereas clMagR favors ferric iron (Fe³⁺) and forms more stable iron-sulfur clusters. Intriguingly, although SQUID magnetometry showed that purified clMagR exhibited approximately five-fold higher mass magnetic susceptibility than hyMagR, its cellular magnetic response was weaker. We hypothesize that the Fe²⁺-preferred intracellular environment associated with hyMagR overexpression primes the cell for enhanced generation of reactive oxygen species (ROS) via the Fenton reaction. Exposure to an SMF synergizes with this primed redox state, triggering the bacterial SOS response and upregulating cell division inhibitors to efficiently induce uniform filamentation. Conclusion Our findings identify the Fe²⁺/Fe³⁺ redox state as a critical determinant of MagR-mediated morphological remodeling and magnetic responsiveness. This discovery suggests a potential strategy for engineering magnetically responsive cellular systems for synthetic biology applications, and provides a plausible framework, which potentially combines intrinsic protein magnetism with redox-state modulation, for further investigating the evolutionary mechanisms of MagR-mediated magnetoreception.

Objective To investigate the diagnostic value of computed tomography (CT) grading in evaluating sacroiliac joint lesions and the extent of joint injury in patients with ankylosing spondylitis (AS) so as to provide evidence-based evidence for CT imaging diagnosis and severity evaluation of AS. Methods A total of 107 patients with AS admitted to the hospital between December 2020 and December 2024 were selected. All patients underwent X-ray and CT examinations, and were graded based on the examination results. The diagnostic value of X-ray and CT in sacroiliac joint lesions and the severity of joint injury in patients with AS was compared. Results The detection rates of osteosclerosis, bone erosion, subchondral bone cystic changes, ankylosis, and soft tissue swelling using CT (90.65%、100.00%、87.85%、41.12%、56.07%、22.43%、33.64%) were higher than those using X-ray (75.70%、84.11%、58.88%、32.71%、48.60%、10.28%、7.48%) (P<0.05). The detection rates of osteosclerosis, bone erosion, subchondral bone cystic changes, joint space narrowing, joint space widening, ankylosis, and soft tissue swelling using CT combined with X-ray (97.20%、10.00%、95.33%、57.94%、73.83%、34.58%、39.25%) were higher than those using CT or X-ray alone (P<0.05). The comparison of the detection of grade I, grade II and grade III joint injury degrees by CT, X-ray and combined examination showed statistically significant differences (P<0.05). The detection rates of grades I and II joint injuries using CT (26.17%、35.51%) were higher than those using X-ray (14.95%、22.43%) (P<0.05). The detection rates of grades 0, I, II, and III joint injury by the combined examination of X-ray and CT were higher than those using X-ray alone (P<0.05). Conclusion CT has greater diagnostic value for sacroiliac joint lesions and severity of joint injury in patients with AS, and allowing for more accurate in AS grading, and combined it with X-ray further improves diagnostic efficacy.

Objective To investigate the diagnostic value of computed tomography (CT) grading in evaluating sacroiliac joint lesions and the extent of joint injury in patients with ankylosing spondylitis (AS) so as to provide evidence-based evidence for CT imaging diagnosis and severity evaluation of AS. Methods A total of 107 patients with AS admitted to the hospital between December 2020 and December 2024 were selected. All patients underwent X-ray and CT examinations, and were graded based on the examination results. The diagnostic value of X-ray and CT in sacroiliac joint lesions and the severity of joint injury in patients with AS was compared. Results The detection rates of osteosclerosis, bone erosion, subchondral bone cystic changes, ankylosis, and soft tissue swelling using CT (90.65%、100.00%、87.85%、41.12%、56.07%、22.43%、33.64%) were higher than those using X-ray (75.70%、84.11%、58.88%、32.71%、48.60%、10.28%、7.48%) (P<0.05). The detection rates of osteosclerosis, bone erosion, subchondral bone cystic changes, joint space narrowing, joint space widening, ankylosis, and soft tissue swelling using CT combined with X-ray (97.20%、10.00%、95.33%、57.94%、73.83%、34.58%、39.25%) were higher than those using CT or X-ray alone (P<0.05). The comparison of the detection of grade I, grade II and grade III joint injury degrees by CT, X-ray and combined examination showed statistically significant differences (P<0.05). The detection rates of grades I and II joint injuries using CT (26.17%、35.51%) were higher than those using X-ray (14.95%、22.43%) (P<0.05). The detection rates of grades 0, I, II, and III joint injury by the combined examination of X-ray and CT were higher than those using X-ray alone (P<0.05). Conclusion CT has greater diagnostic value for sacroiliac joint lesions and severity of joint injury in patients with AS, and allowing for more accurate in AS grading, and combined it with X-ray further improves diagnostic efficacy.

Objective To investigate the diagnostic value of computed tomography (CT) grading in evaluating sacroiliac joint lesions and the extent of joint injury in patients with ankylosing spondylitis (AS) so as to provide evidence-based evidence for CT imaging diagnosis and severity evaluation of AS. Methods A total of 107 patients with AS admitted to the hospital between December 2020 and December 2024 were selected. All patients underwent X-ray and CT examinations, and were graded based on the examination results. The diagnostic value of X-ray and CT in sacroiliac joint lesions and the severity of joint injury in patients with AS was compared. Results The detection rates of osteosclerosis, bone erosion, subchondral bone cystic changes, ankylosis, and soft tissue swelling using CT (90.65%、100.00%、87.85%、41.12%、56.07%、22.43%、33.64%) were higher than those using X-ray (75.70%、84.11%、58.88%、32.71%、48.60%、10.28%、7.48%) (P<0.05). The detection rates of osteosclerosis, bone erosion, subchondral bone cystic changes, joint space narrowing, joint space widening, ankylosis, and soft tissue swelling using CT combined with X-ray (97.20%、10.00%、95.33%、57.94%、73.83%、34.58%、39.25%) were higher than those using CT or X-ray alone (P<0.05). The comparison of the detection of grade I, grade II and grade III joint injury degrees by CT, X-ray and combined examination showed statistically significant differences (P<0.05). The detection rates of grades I and II joint injuries using CT (26.17%、35.51%) were higher than those using X-ray (14.95%、22.43%) (P<0.05). The detection rates of grades 0, I, II, and III joint injury by the combined examination of X-ray and CT were higher than those using X-ray alone (P<0.05). Conclusion CT has greater diagnostic value for sacroiliac joint lesions and severity of joint injury in patients with AS, and allowing for more accurate in AS grading, and combined it with X-ray further improves diagnostic efficacy.

Objective:To compare the changes of maximun flow rate and residual urine volume after tension-free vaginal tape(TVT)and trans-obturator tape(TOT)in the treatment of stress urinary incon-tinence in women.Methods:The clinical data of female patients with stress urinary incontinence who underwent transvaginal midsection tension-free urethral suspension in Peking University People's Hospital from January 2022 to January 2024 were retrospectively analyzed.All the patients were followed up 1 month,6 months and 12 months after surgery.Urodynamics were performed to evaluate urethral sphincter function before surgery.At the same time,B-ultrasonography was improved to determine the residual uri-nary volume of the bladder,and urgent incontinence,detrusor weakness and bladder outlet obstruction were excluded,and the diagnosis was clearly stress incontinence.Maximum flow rate and residual urinary volume were measured during follow-up,and combined with the urinary incontinence questionnaire of the International Urinary Incontinence Advisory Committee,the surgical effect was judged to be cured,im-proved or ineffective according to the degree of improvement of urinary leakage symptoms after surgery.Results:A total of 150 female patients with stress urinary incontinence were included in the study,the average age of the patients was(55.12±10.23)years old,and the follow-up time was 12 months.All patients completed postoperative follow-up,of whom 60 underwent TVT and 90 underwent TOT.The overall effective rates(cure+improvement)1,6,and 12 months after surgery in the TVT group were 93.3％(56/60),91.7％(55/60),and 91.7％(55/60),and those in the TOT group were 92.2％(83/90),90.0％(81/90),90.0％(81/90),respectively,and there was no statistical difference be-tween the two groups.The average maximum urinary flow rates 1,6,and 12 months after surgery in the TVT group were(17.21±4.22)mL/s,(18.05±5.33)mL/s,and(18.37±4.92)mL/s,and those in the TOT group were(18.21±5.32)mL/s,(19.05±4.33)mL/s,and(19.27±4.92)mL/s,re-spectively,and there was no statistical difference between the two groups.The mean residual urine volume 1,6,and 12 months after surgery in the TVT group was(13.21±5.22)mL,(18.25±5.33)mL,and(16.37±7.92)mL,and those in the TOT group was(11.21±6.32)mL,(13.05±5.33)mL,and(11.27±5.92)mL,respectively,and there was no statistical difference between the two groups.Compared with preoperative levels,there were no significant differences in the average maximum flow rate and the residual urine volume in both group at 1,6,and 12 months after surgery.Conclusion:Both TVT and TOT are effective in the treatment of stress incontinence,and have no effect on postopera-tive maximum flow rate and residual urine volume.

OBJECTIVE: To investigate the clinical characteristics and prognosis of patients with IgD multiple myeloma (MM). METHODS: The clinical data of 8 patients with IgD MM admitted to Gansu Provincial Hospital from September 2013 to February 2023 were collected, and their clinical characteristics and prognosis were retrospectively analyzed and summarized. RESULTS: Among the 8 enrolled patients, there were 4 males and 4 females, with a median age of 60 (44-74) years. All patients had symptoms of renal insufficiency and anemia. There were 3 cases of bone invasion, 3 cases of splenomegaly, 7 cases of IgD-λ type, and 1 case of IgD-κ type. FISH examination was performed in 7 cases, and 6 of them were positive for 1q21 . There were 6 cases in DS stage III and 2 cases in DS stage II; According to ISS staging, there were 6 cases in stage III, 1 case in stage II, and 1 case in stage I; According to R-ISS staging, there were 5 cases in stage III and 3 cases in stage II. All patients received bortezomib-based combination chemotherapy, with 1 case undergoing autologous stem cell transplantation (ASCT) and 2 cases receiving daratumumab in combination. The median treatment period was 6 (1-15) cycles. The short-term efficacy was evaluated after 4-6 courses of treatment. Among the 6 patients with assessable efficacy, 1 case experienced disease progression (PD), and 5 cases achieved complete remission (CR). The median follow-up time was 26 (11-33) months, and the median progression-free survival (PFS) and median overall survival (OS) of the patients were 11.25 (3-26) months and 18.5 (4-33) months, respectively. Among the 8 patients, 4 cases died. Among the deceased patients, 3 cases were in R-ISS stage III and 3 cases were 1q21 positive. 2 of the 5 patients with early CR died due to disease progression. CONCLUSION The incidence of IgD MM is low, the symptoms of early renal damage, blood system damage and bone erosion in IgD MM patients are obvious, and the median survival time is short. ASCT and / or daratumumab may bring lasting relief for IgD MM patients, but large-scale clinical studies are still needed.
Humans ; Multiple Myeloma/therapy* ; Middle Aged ; Male ; Female ; Aged ; Prognosis ; Immunoglobulin D ; Adult ; Retrospective Studies

OBJECTIVE: To explore the significance of the plasma cell percentage and immature plasma cells in the prognosis of patients with multiple myeloma (MM). METHODS: The clinical data of 126 newly diagnosed MM patients in Gansu Provincial Hospital from June 2017 to November 2022 were retrospectively analyzed. The enrolled patients were divided into a higher plasma cell percentage group (group A) and a lower plasma cell percentage group (group B) according to the median plasma cell percentage (33.5%). The clinicopathological data of the two groups were compared, and the effect of plasma cell percentage on the prognosis of MM patients was analyzed using survival curves. On this basis, group A and group B were divided into subgroups with immature plasma cells (A1 group, B1 group) and subgroups without immature plasma cells (A2 group, B2 group), respectively, then the survival curves were used to analyze the effect of immature plasma cells on the prognosis of MM patients. RESULTS: Among the 126 patients with MM, the proportions of patients with ISS stage III, elevated β₂-microglobulin(β₂-MG) level, and immature plasma cells in Group A were significantly higher compared those in Group B ( P =0.015, P =0.028, P =0.010). The median overall survival(OS) and progression-free survival(PFS) of group A were 32 months and 10 months, respectively. The median OS of group B was not reached, and the median PFS was 32 months. The 3-year OS rates of patients in group A and group B were 46.7% and 62.2%, respectively ( P =0.021), and the 3-year PFS were 29.2% and 42.5%, respectively ( P =0.033). There were no significant differences in OS and PFS between group A1 and group A2, or between group B1 and group B2 ( P >0.05). Multivariate COX survival analysis showed that the plasma cell percentage ≥33.5%（HR=1.253, 95%CI : 0.580-2.889, P =0.018）, age ≥65 years (HR=2.206, 95%CI : 1.170-3.510, P =0.012), lactate dehydrogenase(LDH) ≥250 U/L (HR=1.180, 95%CI : 0.621-2.398, P =0.048) and β₂-MG ≥3.5 mg/L (HR=1.507, 95%CI : 0.823-3.657, P =0.036) were independent risk factors affecting OS in MM patients. CONCLUSION MM patients with a higher plasma cell percentage (≥33.5%) at the initial diagnosis have a later disease stage, poorer OS and PFS, compared to the patients with a lower percentage(<33.5%) of plasma cells. The presence or absence of immature plasma cells has no significant impact on the survival of MM patients.
Humans ; Multiple Myeloma/pathology* ; Prognosis ; Plasma Cells/cytology* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Aged ; Bone Marrow

OBJECTIVE: To analyze the clinical characteristics and prognosis of patients with T-cell large granular lymphocytic leukemia (T-LGLL). METHODS: The clinical data of 7 patients with T-LGLL in Gansu Provincial Hospital from March 2016 to June 2023 were analyzed retrospectively. RESULTS: Among the 7 patients, 5 were male and 2 were female, with a median age of 51(28-83) years old. At the onset of illness, 6 cases showed symptoms of fatigue and anemia, 4 cases had enlarged lymph nodes, and 5 cases had splenomegaly. Examination showed that 4 cases were antinuclear antibody(ANA) positive, 5 cases were anemia. The median hemoglobin (Hb) level was 83(61-151) g/L, the median white blood cell count (WBC) was 5.6(2.0-8.7)×10⁹ /L, and the median percentage of lymphocytes in peripheral blood was 66.2(13.9-89.1)%. There were 3 cases with extremely active bone marrow hyperplasia, 2 cases with active hyperplasia, and 2 cases with decreased hyperplasia. There were 5 cases with mild myelofibrosis (MF-1), and 1 case with moderate myelofibrosis (MF-2). The median percentage of T cells was 64.3 (31.5-80.6)%. 5 cases showed the classic immunophenotype (CD3 ⁺ CD4^- CD8 ⁺), 6 cases were CD57 ⁺, 3 cases were TCRα/β ⁺, and 3 cases were TCRγ/δ ⁺. TCRG rearrangement was detected in 5 cases.The median follow-up time was 55(4-87) months, one patient died of heart disease, and the other 6 patients are surviving. CONCLUSION The incidence of T-LGLL is low. The initial symptoms of T-LGLL include anemia, fatigue, lymph node enlargement, splenomegaly, and higher percentage of lymphocytes in peripheral blood, the percentage of abnormal T cells in bone marrow was significantly increased. Analysis of flow cytometric immunophenotyping, TCR gene rearrangement, and hot spot genes such as STAT3 and STAT5b, can improve the diagnostic accuracy.
Humans ; Leukemia, Large Granular Lymphocytic/diagnosis* ; Male ; Middle Aged ; Female ; Aged ; Prognosis ; Adult ; Aged, 80 and over ; Retrospective Studies

OBJECTIVE: To explore the key target molecules and potential mechanisms of oridonin against non-small cell lung cancer (NSCLC). METHODS: The target molecules of oridonin were retrieved from SEA, STITCH, SuperPred and TargetPred databases; target genes associated with the treatment of NSCLC were retrieved from GeneCards, DisGeNET and TTD databases. Then, the overlapping target molecules between the drug and the disease were identified. The protein-protein interaction (PPI) was constructed using the STRING database according to overlapping targets, and Cytoscape was used to screen for key targets. Molecular docking verification were performed using AutoDockTools and PyMOL software. Using the DAVID database, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted. The impact of oridonin on the proliferation and apoptosis of NSCLC cells was assessed using cell counting kit-8, cell proliferation EdU image kit, and Annexin V-FITC/PI apoptosis kit respectively. Moreover, real-time quantitative PCR and Western blot were used to verify the potential mechanisms. RESULTS: Fifty-six target molecules and 12 key target molecules of oridonin involved in NSCLC treatment were identified, including tumor protein 53 (TP53), Caspase-3, signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase kinase 8 (MAPK8), and mammalian target of rapamycin (mTOR). Molecular docking showed that oridonin and its key target molecules bind spontaneously. GO and KEGG enrichment analyses revealed cancer, apoptosis, phosphoinositide-3 kinase/protein kinase B (PI3K/Akt), and other signaling pathways. In vitro experiments showed that oridonin inhibited the proliferation, induced apoptosis, downregulated the expression of Bcl-2 and Akt, and upregulated the expression of Caspase-3. CONCLUSION Oridonin can act on multiple targets and pathways to exert its inhibitory effects on NSCLC, and its mechanism may be related to upregulating the expression of Caspase-3 and downregulating the expressions of Akt and Bcl-2.
Diterpenes, Kaurane/chemistry* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Humans ; Network Pharmacology ; Lung Neoplasms/pathology* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Molecular Docking Simulation ; Protein Interaction Maps/drug effects* ; Cell Line, Tumor ; Signal Transduction/drug effects* ; Gene Expression Regulation, Neoplastic/drug effects* ; Reproducibility of Results ; Gene Ontology